High-dose Chemotherapy With Autologous Stem Cell Transplantation Research Articles

The role of autologous stem-cell transplantation in classical Hodgkin lymphoma in the modern era

Despite excellent cure rates with modern front-line regimens, up to 20% of patients with Hodgkin lymphoma will progress through front-line therapy or experience disease relapse. Worldwide, salvage chemotherapy followed by high-dose chemotherapy with autologous stem cell transplantation (HDT/ASCT) is considered the standard of care for these patients and can cure approximately 50% of relapsed or refractory (R/R) patients in the second line. Brentuximab vedotin (BV), an anti-CD30 antibody drug conjugate, and PD1 inhibitors like nivolumab and pembrolizumab, have high response rates in patients who recur after HDT/ASCT. When used prior to HDT/ASCT, BV and PD1 inhibitors appear to dramatically increase the effectiveness of salvage therapies with complete response rates often double those seen with historic chemotherapy-based regimens and durable progression free survival (PFS) post-HDT/ASCT. Emerging data in adults and from pediatric trials showing a durable PFS in a subset of relapsed patients raises the question of whether HDT/ASCT is essential for cure in R/R patients after PD1 based salvage. Future studies will help clarify if ASCT can omitted PD1 based salvage to avoid the potential toxicity of HDT/ASCT without compromising cure.

Sarcopenia with decreased total psoas muscle area in children with high-risk neuroblastoma

BackgroundWe calculated psoas muscle area (PMA) z-scores in high-risk neuroblastoma patients undergoing treatment to examine the clinical significance of sarcopenia in this cohort. MethodsWe analyzed retrospective data from patients aged 0–18 who were diagnosed with abdominal neuroblastoma between 2005 and 2019 at Samsung Medical Center. Patients categorized as high-risk undergone induction chemotherapy, neuroblastoma excision, and tandem high-dose chemotherapy with autologous stem cell transplantation (HDCT/auto-SCT) were selected. L3-4 lumbar levels on axial CT images were identified and we measured the areas of the left and right psoas muscles to determine tPMA. Total PMA z-scores were calculated using an open online tool. ResultsThere were 45 boys and 25 girls with a mean age of 3.86 years. CT images taken at initial diagnosis and after tandem HDCT/auto-SCT were selected to calculate tPMA z-scores. Mean elapsed time between the two measurements was 12.91 ± 1.73 months. Mean tPMA z-score significantly decreased from −0.21 ± 1.29 to −0.66 ± 0.97 (p = 0.022). Length of hospital stay was significantly longer in the group of patients whose tPMA z-scores decreased by more than .45 (177.62 ± 28.82 days vs. 165.75 ± 21.34 days, p = 0.049). Presence of sarcopenia at initial diagnosis was a significant risk factor for bacterial infection during neuroblastoma treatment.Conclusion: tPMA z-scores in high-risk neuroblastoma patients decreased significantly following a treatment regimen that included induction chemotherapy, tumor resection surgery, and HDCT/auto-SCT. A greater decrease in tPMA z-score was associated with longer hospital stay during treatment.

High-dose chemotherapy with autologous stem-cell transplantation for relapsed metastatic germ cell tumors The Alberta experience.

High-dose chemotherapy with autologous stem-cell transplantation (HDC-ASCT) is standard therapy for metastatic germ cell tumors (mGCTs) in patients whose disease progresses during or after conventional chemotherapy. We conducted a retrospective review of HDC-ASCT in relapsed mGCT patients in the province of Alberta, Canada, over the past two decades. Patients with mGCTs who received HDC-ASCT at two provincial cancer referral centers from 2000-2018 were identified from institutional databases. Baseline clinical and treatment characteristics were collected, as well as overall survival (OS ) and disease-free survival (DFS). Relevant prognostic variables were analyzed. Forty-three patients were identified. The median age was 28 years (range 19-56). A majority (95%) had non-seminoma histology and testis/retroperitoneal primary (84%). Twenty patients (47%) had poor-risk disease, as per The International Germ Cell Consensus Classification (IGCCC), at start of first-line chemotherapy. HDC-ASCT was used as second-line therapy in 65% of patients, and 58% of ASCT patients received tandem transplants. Median followup after ASCT was 22 months (range 2-181). At last followup, 42% of patients were alive without disease, including 3/7 (43%) of patients with primary mediastinal disease. Two-year and five-year DFS/OS ratios were 44%/65% and 38%/45%, respectively. Median OS and DFS for all patients were 30.0 months (13.3-46.6) and 8.0 months (0.9-15.1), respectively. We found that HDC-ASCT is an effective salvage therapy in mGCT, consistent with existing literature. Patients appeared to benefit regardless of primary site. Although limited by small sample size, we found a numerical difference in DFS and OS between second- and third-line HDC-ASCT and single vs. tandem ASCT.

AUTOLOGOUS HEMATOPOIETIC CELL TRANSPLANTATION FOR PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA (PCNSL). REAL‐WORLD REPORT OF POLISH LYMPHOMA RESEARCH GROUP.

Introduction: High-dose chemotherapy with autologous stem-cell transplantation (HDC-ASCT) is now the preferred consolidation strategy for young PCNSL patients. The optimal conditioning regimen is unknown. The data suggests that BEAM (carmustine, etoposide, cytarabine, melphalan) is ineffective, BCNU/TT (carmustine/thiotepa) is well-tolerated with treatment related mortality (TRM) 1%–3%, but late relapses are common, and TBC (thiotepa, busulfan, cyclophosphamide) is highly effective but with higher TRM 11%. Methods: The aim of the study was to analyze the safety and efficacy of consolidation based on conditioning regimen consisted of carmustine, etoposide and thiotepa (BET)1 followed by ASCT. We evaluated the outcome of 45 immunocompetent adult patients with PCNSL treated in 4 Polish centers between Feb. 2015 and Oct. 2022. Six cycles of induction with rituximab, methotrexate (3.5 g/m2), ifosfamide and vincristine (R-MIV) and one cycle of cytarabine with thiotepa (AT)2 were given. Patients with a complete or partial response (CR/PR) proceeded to consolidation with carmustine 400 mg/m2 on day -5, etoposide 150 mg/m2 on day -5,-4, -3, and thiotepa 5 mg/kg every 12 h on days -4 and -3 (total 4 doses), followed by ASCT. Results: Median age (range) of 45 transplanted patients was 57 years (19-66) with 15 (33%) patients ≥60 years old. At the end of induction 29 (64.5%) patients obtained CR/CRun (19/10 respectively), with additional 5 (11%) patients with no evidence of disease at baseline, and 11 (24.5%) in PR, based on standard CT/MRI assessment. For 32 (71%) patients with 18FDG PET/CT done before ASCT, metabolic-CR was confirmed. Mean (range) number of 584.4 (187–2642) × 106 CD34+ peripheral blood stem cells were collected, corresponding to 7.2 × 106 cells/kg (2.55–34.7 × 106 cells/kg). Mean hospitalization time from the day of ASCT was 15 days. Mean time to hematologic recovery with PLT > 25 G/L and NEU > 0.5/ > 1.0 G/L was 9 and 9/10 days, respectively. The most common grade 3–4 non-haematological toxicities were diarrhea (12 patients, mean 4 days) and mucositis (18 patients, mean 5 days). Febrile neutropenia occurred in 21 patients (mean 2.5 days). Blood cultures did not reveal any relevant pathogens except one patient with confirmed Enterobacter cloacae-ESBL and Klebsiella oxytoca. Two patients (TRM 4.4%) died of transplant-related complications: septic shock and neurotoxicity. At a median (range) follow-up of 41 (13-92) months, 3-year progression free survival (PFS) and overall survival (OS) was 78% (95% CI: 65-91) and 81% (95% CI: 68-93). Relapse occurred in 9 patients, in all but one within first 11 months after ASCT. Causes of death were: lymphoma progression (n = 6), TRM (n = 2), accident (n = 1) and concomitant diseases (n = 2). Keywords: aggressive B-cell non-Hodgkin lymphoma, stem cell transplant No conflicts of interests pertinent to the abstract.

Late effects in patients with mantle cell lymphoma treated with or without autologous stem cell transplantation.

Studies on late effects in patients with mantle cell lymphoma (MCL) are becoming increasingly important as survival is improving, and novel targeted drugs are being introduced. However, knowledge about late effects is limited. The aim of this population-based study was to describe the magnitude and panorama of late effects among patients treated with or without high-dose chemotherapy with autologous stem cell transplantation (HD-ASCT). The study cohort included all patients with MCL, recorded in the Swedish Lymphoma Register, aged 18 to 69 years, diagnosed between 2000 and 2014 (N= 620; treated with HD-ASCT, n= 247) and 1:10 matched healthy comparators. Patients and comparators were followed up via the National Patient Register and Cause of Death Register, from 12 months after diagnosis or matching to December 2017. Incidence rate ratios of the numbers of outpatient visits, hospitalizations, and bed days were estimated using negative binomial regression models. In relation to the matched comparators, the rate of specialist and hospital visits was significantly higher among patients with MCL. Patients with MCL had especially high relative risks of infectious, respiratory, and blood disorders. Within this observation period, no difference in the rate of these complications, including secondary neoplasms, was observed between patients treated with and without HD-ASCT. Most of the patients died from their lymphoma and not from another cause or treatment complication. Taken together, our results imply that most of the posttreatment health care needs are related to the lymphoma disease itself, thus, indicating the need for more efficient treatment options.

High-dose chemotherapy with autologous stem cell transplantation for patients with extracranial germ cell tumors – experience of two Brazilian pediatric centers

Malignant extracranial germ cell tumors (GCTs) are rare in pediatric patients and are usually extremely sensitive to chemotherapy. Relapsed or refractory tumors, although rare, established the need for second-line therapies, including high-dose chemotherapy with autologous stem cell transplantation (HDCT/ASCT). However, there are few data on its use in children with GCTs. We present a retrospective analysis of all patients diagnosed with extracranial GCTs who received HDCT/ASCT at two Brazilian pediatric cancer centers from May 1999 to December 2019. We identified a total of 34 patients with a median age at diagnosis of 2.8 years (range, 0 to 18.8), who received HDCT/ASCT. Most patients (73%) received carboplatin, etoposide and melphalan (CEM) as a HDCT regimen. Fourteen patients received a second-line conventional dose chemotherapy (CDCT), 14 received a third-line CDCT and five received even a fourth-line CDCT prior to HDCT/ASCT. After a median follow-up of 22.7 months (range, 0.3 to 198.1), 16 patients had died after tumor relapse/progression and 2 patients died from HDCT/ASCT toxicity. We observed a 5-year OS of 47.1% and 5-year EFS of 44.1%. The 5-year OS for patients referred for HDCT/ASCT with progressive disease was 10% compared to 62.5% for those who achieved disease control before HDCT/ASCT (p = 0.001). In our experience, heavily pretreated children and adolescents with extracranial GCTs achieved considerable survival rates with HDCT/ASCT since, at least, partial control of their disease was possible before starting HDCT/ASCT. The role of HDCT/ASCT in pediatric patients with GCTs should be investigated in prospective trials.

Survival, prognostic factors, hospitalization time and clinical performance status after first cerebral relapse or progression in 54 patients with primary CNS lymphoma not eligible for high dose chemotherapy: a retrospective analysis

BackgroundTreatment of relapsed or refractory primary CNS lymphoma (r/r PCNSL) is difficult, particularly in patients not eligible for high dose chemotherapy with autologous stem cell transplantation (HDC-ASCT). No standard treatment has been defined for these patients yet.MethodsWe retrospectively analyzed survival, prognostic factors, hospitalization time and Karnofsky performance score (KPS) before and after treatment in 54 r/r PCNSL patients with isolated cerebral relapse or progression (n = 23 refractory, n = 31 relapsed) not eligible for HDC-ASCT, who received heterogenous salvage treatments.ResultsTreatments were temozolomide (+ rituximab) (n = 21), high dose methotrexate (HD-MTX)-based therapy (n = 11), whole brain radiotherapy (WBRT)/focal radiotherapy (n = 11), other systemic treatments (n = 2) and best supportive care (BSC, n = 9). Median progression free survival (PFS) and overall survival (OS) were 2.6 months (95% CI 1.0–4.2 months) and 4.8 months (95% CI 3.3–6.3 months), respectively. Eight patients survived for ≥ 3 years (13.1%, n = 3 received temozolomide, n = 3 WBRT, n = 2 HD-MTX-based treatment). Application of any salvage treatment (vs. BSC), younger age at relapse and asymptomatic (vs. symptomatic) relapse were positive prognostic factors. No significant differences in OS were found for the different salvage treatments. Median hospitalization time for treatment was 15/13 days for temozolomide (+ rituximab)/radiotherapy compared to 55 days for HD-MTX-based therapy. Median KPS in assessable patients (n = 41) was 60 (range 30–100) before treatment and 50 (range 20–90) after treatment. In patients with response to treatment (n = 16) KPS improved from 60 (range 40–90) before treatment to 70 (range 50–90) after treatment, while patients with PD (n = 25) deteriorated from 60 (range 30–100) to 40 (range 20–70).ConclusionSurvival for this cohort of r/r PCNSL patients with isolated cerebral relapse or progression was poor. Considering long hospital stays associated with HD-MTX-based chemotherapy and neurotoxicity associated with WBRT, temozolomide might be worth considering with a chance of prolonged survival and avoidance of long hospitalization. Novel therapeutic agents are urgently needed to improve survival in r/r PCNSL patients.

High‐dose chemotherapy followed by autologous stem cell transplantation in pediatric patients with relapsed osteosarcoma

Patients with relapsed osteosarcoma have poor treatment outcomes. High-dose chemotherapy with autologous stem cell transplantation (HDCT/ASCT) has been used in several high-risk malignant solid tumors; however, few studies have evaluated their role in treating osteosarcoma. We evaluated the effectiveness of HDCT/ASCT in relapsed pediatric osteosarcoma cases. We retrospectively reviewed the medical records of 40 patients diagnosed with and treated for relapsed osteosarcoma at Asan Medical Center and Samsung Medical Center from January 1996 to July 2019. The median age of this cohort was 13.4years (range: 6.1-18.2). The cohort's 5-year overall survival (OS) was 51.0%±0.1% during a median follow-up period of 67.5months. Twenty-five patients (62.5%) achieved complete remission (CR) with salvage treatment, and the 5-year OS was 82.4%±0.1%, whereas none of the remaining 15 patients who did not achieve CR survived (p<.0001). Of the 25 CR cases, 15 underwent subsequent HDCT/ASCT. We compared the effect of HDCT/ASCT among patients who achieved CR. There were no significant differences in the 5-year OS outcomes between patients who did and did not receive HDCT/ASCT (83.9%±0.1%, 13/15 vs. 80.0%±0.1%, 8/10, respectively; p=.923). To our knowledge, we report the first comparative cohort study that proved HDCT/ASCT does not significantly improve survival outcomes in relapsed osteosarcoma. Achievement of CR remains the most crucial factor for good survival outcomes.

Isolated intraocular relapses of primary cerebral lymphomas: An LOC network study.

Most relapses of primary central nervous system lymphoma (PCNSL) occur in the brain and are associated with a poor prognosis. Isolated intraocular relapses (IIORs) are rare and poorly described. We retrospectively selected from the French Lymphome Oculo-Cérébral database PCNSL patients who initially presented with cerebral localization and who experienced IIOR during the course of the disease. Of the 1472 patients included in the database, 55 patients presented an IIOR. Their median age was 68years, and median Karnofsky Performance Status 80. IL-10 levels in the aqueous humor and/or in the vitreous were increased in 42/46 patients. 45/55 patients received systemic chemotherapy, and 11/55 received high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) as consolidation treatment. After a median follow-up of 69months, 42/55 patients had relapsed, including 90% of the patients who did not receive HCT-ASCT at IIOR and 40% of the patients who received HCT-ASCT at IIOR (p<0.001). The first relapse after the initial IIOR was exclusively in the eye in 23/42 patients, and 29/42 patients had a subsequent brain relapse during the course of the disease. The median progression-free survival, brain-free survival and overall survival from IIOR were 12.2, 48.6 and 57.1months, respectively. Isolated intraocular relapse is not exceptional in the course of PCNSL and deserves systematic ophthalmological follow-up. Its prognosis is much better than the prognosis of brain relapse, with an evolution close to that of primary vitreoretinal lymphoma. With the exception of patients who received HCT-ASCT at IIOR, almost all patients subsequently relapsed, often with other IIORs.

High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation in Relapsed or Refractory Primary CNS Lymphoma: A Retrospective Monocentric Analysis of Long-Term Outcome, Prognostic Factors, and Toxicity.

Simple SummaryNo standard treatment is defined for relapsed or refractory (r/r) primary CNS lymphoma (PCNSL). However, high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT), an efficient first line treatment in younger PCNSL patients, is commonly applied in relapsed or refractory disease, if tolerable. Here, we retrospectively analyzed 59 patients with r/r PCNSL focusing specifically on differences in long-term outcome and toxicity in patients <65 years (n = 33) and ≥65 years (n = 26) of age.High-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) is reportedly an effective treatment strategy in relapsed or refractory primary CNS lymphoma (r/r PCNSL); however, only selected patients are eligible for this treatment. We retrospectively analyzed outcome, prognostic factors, and toxicity in 59 patients with r/r PCNSL planned to receive HCT-ASCT at our institution between January 2005 and December 2021 (n = 33 < 65 years; n = 26 ≥ 65 years). Median follow-up was 65 months (95% CI 21–109). Median age was 63 years (range 29–76), median Karnofsky performance score (KPS) was 80 (range 30–100). In the entire cohort of 59 patients, median overall survival (OS) was 14 months (95% CI 0–37). In 50/59 (84.7%) patients who completed HCT-ASCT, median progression free survival (PFS) was 12 months (95% CI 3–21) and median OS 30 months (95% CI 0–87). 1-year, 2-year, and 5-year OS rates of 61.2%, 52.3% and 47.1%, respectively, were observed. Six patients (10.2%) died related to treatment (1 during induction treatment, 5 post HCT-ASCT). Age was not prognostic. On univariate analysis, KPS ≥ 80 (p = 0.019) and complete or partial remission before HCT-ASCT (p = 0.026) were positive prognosticators of OS; on multivariate analysis, KPS (p = 0.043) and male gender (p = 0.039) had an impact on OS. The 5-year OS rate in patients with progressive or stable disease after induction treatment was 32.7%. In summary, HCT-ASCT was effective and feasible in this cohort of r/r PCNSL patients. Clinical state, remission status before HCT-ASCT, and gender influenced survival, whereas age did not influence outcome in this study.

Significance of maintenance therapy after HDT/ASCT in symptomatic multiple myeloma: A multicenter retrospective analysis in Kansai Myeloma Forum.

A total of 129 symptomatic patients with multiple myeloma (MM) who underwent high‐dose chemotherapy with autologous stem cell transplantation (HDT/ASCT) were analyzed. The 4‐year overall survival (OS) of patients with maintenance (n = 82) was 80%, whereas that of patients without maintenance (n = 47) was 72% (p = 0.426). The 4‐year progression‐free survival (PFS) of patients with maintenance was 38%, whereas that of patients without maintenance was 27% (p = 0.088). Multivariate analysis revealed that an International Staging System score ≥2 was associated with worse PFS (hazard ratio 1.62, p = 0.043). Among the 129 patients, two were excluded owing to early relapse, 50 patients achieved complete response (CR), and 77 patients failed to achieve CR. Patients who achieved CR showed better 4‐year PFS than those who failed to achieve CR (41% vs. 30%, p = 0.027); however, 4‐year OS was not different (76% vs. 82%, p = 0.971). In patients who achieved CR, 4‐year OS with/without maintenance was 74%/81% (p = 0.357), 4‐year PFS with/without maintenance was 42%/40% (p = 0.954). In patients who failed to achieve CR, the 4‐year OS with/without maintenance was 97%/91% (p = 0.107), and 4‐year PFS with/without maintenance was 36%/16% (p < 0.001). In patients who failed to achieve CR, maintenance significantly improved the PFS. Maintenance after HDT/ASCT can prolong PFS in patients who fail to achieve CR in real‐world settings.

P14.48 Extracerebral relapses of primary CNS lymphoma (PCNSL): a LOC network retrospective study

Abstract BACKGROUND Classically PCNSL remain confined within the CNS throughout their evolution for reasons still unknown (&amp;gt; 80% cerebral relapses). The aim of this study was to describe the characteristics and outcomes of the rare extracerebral relapses of PCNSL. MATERIAL AND METHODS This is a multicenter, retrospective study. We included all immunocompetent patients newly diagnosed with diffuse large B-cell PCNSL registered in the national LOC network database since 2010 and followed prospectively, who presented an extracerebral relapse, pure (extracerebral only site) or associated with concomitant CNS relapse (mixed). All had body scan and/or TEP -CT at diagnosis work up. RESULTS Of the 1968 PCNSL included in the database, 29 (1.5%) patients presented a systemic relapse [median age 71 years, median KPS 70% at relapse], either pure (n=19) or mixed (n=10), with a histological confirmation in 19 cases (66%). The median delay between initial diagnosis and systemic relapse was 15 months [2–49 months], with 5 very early relapses (&amp;lt;8 months) and 10 late relapses (&amp;gt;21 months). 27 patients had symptoms, 21 related to the location of relapse and 6 with only general symptoms. The localization was thoracic (n=11), abdominal/pelvic (n=14), head/neck (n=6) and limbs (n=9). We found visceral (n=24, 83%), including testis in 5 (28%) men and breast in 3 (27%) women, lymph node (n=12, 41%) and peripheral nervous system (PNS) (n=8, 28%; 4 plexus and 4 extradural roots) involvement. 27 patients were treated with chemotherapy, either with only systemic target (n=8) (R-CHOP alone) or mixed systemic and CNS target (n=19) (R-CHOP-MTX, R-ICE, GEMOX, RDHAC) and consolidated by high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) in 4 cases [median age 55 years, median KPS 80%], with 34% of complete response. After systemic relapse, median progression-free survival was 8 months and overall survival (OS) was 9 months, 15 months for pure systemic and 4.5 months for mixed relapses. KPS&amp;gt;70%, pure systemic relapses and complete response were significantly associated with higher OS in univariate analysis. CONCLUSION Extracerebral PCNSL relapses are very rare, mainly extranodal and involve a large spectrum of anatomical sites, the most frequent being testis, breast and PNS. Prognosis was worse in case of mixed relapse than in pure systemic relapse that was similar to non PCNSL lymphomas. Very early relapses raise the question of misdiagnosed occult extracerebral lymphoma at diagnostic work up that should include systematically a FDG PET-CT. More studies are needed to refine their treatment and to specify the role of HCT-ASCT. Paired tumor tissues at diagnosis (CNS)/relapse (extracerebral) analysis would provide a better understanding of underlying molecular mechanisms.

Post-treatment work patterns amongst survivors of lymphoma treated with high-dose chemotherapy with autologous stem-cell transplantation

BackgroundThis study describes post-treatment work patterns in lymphoma survivors treated with high-dose chemotherapy with autologous stem-cell transplantation (HDT-ASCT). It aims to identify determinants for labour force participation and exclusion after HDT-ASCT.MethodsAll survivors treated with HDT-ASCT for lymphoma in Norway between 1995 and 2008, aged ≥18 years at HDT-ASCT and alive at survey in 2012–2013 were eligible. We divide survivors by current employment status (full-time, part-time and unemployed). Main outcomes are current employment status, work hours and work ability. Withdrawals are patients employed when diagnosed but not before HDT-ASCT.ResultsOf the 274 who completed the survey, 82% (N = 225) were included in the final analyses. Mean age at survey was 52 years, 39% were female, 85% were employed when diagnosed, 77% before HDT-ASCT and 69% at survey. Employment before HDT-ASCT corresponds with a higher probability of employment at survey for a given symptom burden. In the most extensive statistical model, it increases with 37.3 percentage points. Work hours amongst withdrawals plummet after HDT-ASCT while work ability shows a rebound effect. The potential economic gain from their re-enter into the work force equals 70% of the average annual wage in Norway in 2012.ConclusionsFor a given symptom burden, staying employed throughout diagnosis and treatment is associated with a higher probability of future employment. These results favour policies for labour force inclusion past diagnosis and treatment increasing cancer survivors’ probability of future employment. However, we need more research on withdrawal mechanisms, and on policy measures that promote inclusion.

High-dose chemotherapy with autologous stem cell transplantation (HDC-ASCT) for relapsed metastatic germ cell tumors (mGCTs): The Alberta experience from 2001 to 2018.

406 Background: HDC-ASCT is a standard therapy for patients (pts) with mGCTs whose disease progresses on or after conventional dose chemotherapy. We conducted a retrospective review of HDC-ASCT in pts with relapsed mCGT in Alberta over the past two decades. Methods: Pts with mGCTs who received HDC-ASCT at two provincial referral cancer centers in Alberta, Canada from 2001-2018 were identified. Baseline clinical and treatment characteristics were collected as well as overall survival (OS) and disease-free survival (DFS). Relevant prognostic variables were analyzed. Results: Forty three pts were identified. Median age was 28 years (range 19 – 56). Majority (95%) had non-seminoma histology and testis/retroperitoneal primary (84%). Twenty pts (47%) had poor risk disease as per IGCCC at start of first-line chemotherapy. HDC-ASCT was used as second-line therapy in 65% and 58% received tandem HDC-ASCT. Median follow-up from ASCT was 22 months (range 2 – 181). At last follow-up, 42% of pts are alive without disease, including 3/7 (43%) of pts with primary mediastinal disease. Two-year and 5-year DFS/OS were 44%/51% and 41%/43%, respectively. Median OS and DFS for all pts were 27.9 months (10.2 – NR) and 9.3 months (4.2 – 124), respectively. Conclusions: We found that HDC-ASCT is an effective salvage therapy in mGCT, consistent with existing literature. Pts appeared to benefit regardless of primary site. Though limited by small sample size, we found a numerical difference in DFS and OS between 2nd and 3rd line HDC-ASCT and single vs. tandem ASCT.[Table: see text]

Management and outcome of primary CNS lymphoma in the modern era: An LOC network study.

Real-life studies on patients with primary CNS lymphoma (PCNSL) are scarce. Our objective was to analyze, in a nationwide population-based study, the current medical practice in the management of PCNSL. The French oculo-cerebral lymphoma network (LOC) database prospectively records all newly diagnosed PCNSL cases from 32 French centers. Data of patients diagnosed between 2011 and 2016 were retrospectively analyzed. We identified 1,002 immunocompetent patients (43% aged >70 years, median Karnofsky Performance Status [KPS] 60). First-line treatment was high-dose methotrexate-based chemotherapy in 92% of cases, with an increasing use of rituximab over time (66%). Patients <60 years of age received consolidation treatment in 77% of cases, consisting of whole-brain radiotherapy (WBRT) (54%) or high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) (23%). Among patients >60 years of age, WBRT and HCT-ASCT consolidation were administered in only 9% and 2%, respectively. The complete response rate to initial chemotherapy was 50%. Median progression-free survival was 10.5 months. For relapse, second-line chemotherapy, HCT-ASCT, WBRT, and palliative care were offered to 55%, 17%, 10%, and 18% of patients, respectively. The median, 2-year, and 5-year overall survival was 25.3 months, 51%, and 38%, respectively (<60 years: not reached [NR], 70%, and 61%; >60 years: 15.4 months, 44%, and 28%). Age, KPS, sex, and response to induction CT were independent prognostic factors in multivariate analysis. Our study confirms the increasing proportion of elderly within the PCNSL population and shows comparable outcome in this population-based study with those reported by clinical trials, reflecting a notable application of recent PCNSL advances in treatment.

PB2377 SECONDARY HYPOGAMMAGLOBULINEMIA AFTER HIGH DOSE CHEMOTHERAPY WITH AUTOLOGOUS STEM CELL TRANSPLANTATION FOR LYMPHOMA

Background:Secondary hypogammaglobulinemia is associated with hematological malignancy, particularly related to lymphoid malignancy. Other than malignancy itself, treatments induce iatrogenic hypogammaglobulinemia. In standard, eligible patients with advanced lymphoma receive high dose chemotherapy with autologous stem cell transplantation (HDT/ASCT). However, frequency and risk of hypogammaglobulinemia in auto‐setting is unknown.Aims:To clarify frequency and risk of hypogammaglobulinemia in auto‐setting.Methods:We retrospectively analyzed 101 patients with advanced lymphoma who received HDT/ASCT at Kansai Medical University Hospital and Kansai Medical University Medical Center from August 2006 to September 2018. All patients received MEAM regimen with/without rituximab as a conditioning.Results:Median age was 59(24‐71) y/o. Among 101 patients, 92% of patients(n = 93) was measured immunoglobulin levels routinely. 52% of patients(n = 53) had hypogammaglobulinemia(IgG &lt; 700 mg/dl) and 25%(n = 25) of patients remains hypogammaglobulinemia presently. 14 patients recovered from hypogammaglobulinemia. Median period to recovery was 28(0.7‐56.8)months. Among the patients developed hypogammaglobulinemia, 87% was with B cell lymphoma, 9% with T cell lymphoma and 4% with Hodgkin lymphoma. Severe infection(≥grade3) was seen in 16 patients. The most frequent infection was bacterial infection unknown species(n = 5), followed HBV reactivation(n = 3) and Herpes zoster(n = 3), and BKV(n = 2).Summary/Conclusion:52% of patients had hypogammaglobulinemia after HDT/ASCT, which was not only with B cell lymphoma but also with T cell and Hodgkin lymphoma. Median period of immunoglobulin recover is over one year. Addition to common bacterial infections, we should be careful about virus infections.

Risk factors and timing of autologous stem cell transplantation for patients with peripheral T-cell lymphoma.

High-dose chemotherapy with autologous stem cell transplantation (HDC-ASCT) is an option for patients with peripheral T-cell lymphoma (PTCL); however, neither prospective nor retrospective studies support proceeding with ASCT upfront, and the timing of HDC-ASCT remains controversial. We retrospectively analyzed the risk factors for outcomes of 570 patients with PTCL, including PTCL not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL), who received ASCT for frontline consolidation (n = 98 and 75, respectively) or alternative therapies after either relapse (n = 112 and 75) or primary induction failure (PIF; n = 127 and 83) between 2000 and 2015. Significant risk factors for overall survival (OS) after upfront ASCT were a ≥ 2 prognostic index for T-cell lymphoma (P < 0.001) and partial response (PR) at ASCT (P = 0.041) in PTCL-NOS patients, and > 60years of age (P = 0.0028) and PR at ASCT (P = 0.0013) in AITL patients. Performance status of ≥ 2at ASCT (P < 0.001), receiving ≥ 3 regimens before ASCT (P = 0.018), and PR at ASCT (P = 0.018) in PTCL-NOS patients and > 60years of age at ASCT (P = 0.0077) in AITL patients were risk factors for OS after ASCT with a chemosensitive PIF status. Strategies that carefully select PTCL patients may allow identification of individuals suitable for ASCT.

The Diagnosis and Treatment of Primary CNS Lymphoma.

Primary central nervous system lymphoma is a diffuse large B-celllymphoma with exclusive manifestation in the central nervous system (CNS), leptomeninges, and eyes. Its incidence is 0.5 per 100 000 persons per year.Currently, no evidence-based standard of care exists. This review is based on pertinent publications (2000-2017) retrieved by aselective search in PubMed. The clinical and neuroradiological presentation of primary CNS lymphoma isoften nonspecific, and histopathological confirmation is obligatory. The disease, if left un- treated, leads to death within weeks or months. If the patient's general condition permits, treatment should consist of a high-dose chemotherapy based on methotrexate (HD- MTX) combined with rituximab and other cytostatic drugs that penetrate the blood-brain barrier. Long-term survival can be achieved in patients under age 70 by adding non- myeloablative consolidation chemotherapy or high-dose chemotherapy with autologous stem cell transplantation (HD-AST) to the induction therapy. Clinical trials comparing the efficacy and toxicity of these two treatment strategies are currently underway. Con- solidation whole-brain radiotherapy is associated with the risk of severe neurotoxicity and should be reserved for patients who do not qualify for systemic treatment. Some 30% of patients are refractory to primary treatment, and at least 50% relapse. In patients who are still in good general condition, relapse can be managed with HD-AST. Re- exposure to conventional HD-MTX-based polychemotherapy is another option, if the initial response was durable. The 5-year survival rate of all treated patients is 31%,according to registry data. Current recommendations for the treatment of primary CNS lymphomaare based on only a small number of prospective clinical trials. Patients with this disease should be treated by interdisciplinary teams in experienced centers, andpreferably as part of a controlled trial.

High-dose chemotherapy with autologous haemopoietic stem cell transplantation for newly diagnosed primary CNS lymphoma: a prospective, single-arm, phase 2 trial

High-dose methotrexate-based chemotherapy is standard for primary CNS lymphoma, but most patients relapse. High-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) is supposed to overcome the blood-brain barrier and eliminate residual disease in the CNS. We aimed to investigate the safety and efficacy of HCT-ASCT in patients with newly diagnosed primary CNS lymphoma. In this prospective, single-arm, phase 2 trial, we recruited patients aged 18-65 years with newly diagnosed primary CNS lymphoma and immunocompetence, with no limitation on clinical performance status, from 15 hospitals in Germany. Patients received five courses of intravenous rituximab 375 mg/m(2) (7 days before first high-dose methotrexate course and then every 10 days) and four courses of intravenous high-dose methotrexate 8000 mg/m(2) (every 10 days) and then two courses of intravenous rituximab 375 mg/m(2) (day 1), cytarabine 3 g/m(2) (days 2 and 3), and thiotepa 40 mg/m(2) (day 3). 3 weeks after the last course, patients commenced intravenous HCT-ASCT (rituximab 375 mg/m(2) [day 1], carmustine 400 mg/m(2) [day 2], thiotepa 2 × 5 mg/kg [days 3 and 4], and infusion of stem cells [day 7]), irrespective of response status after induction. We restricted radiotherapy to patients without complete response after HCT-ASCT. The primary endpoint was complete response at day 30 after HCT-ASCT in all registered eligible patients who received at least 1 day of study treatment. This trial is registered at ClinicalTrials.gov, number NCT00647049. Between Jan 18, 2007, and May 23, 2011, we recruited 81 patients, of whom two (2%) were excluded, therefore we included 79 (98%) patients in the analysis. All patients started induction treatment; 73 (92%) commenced HCT-ASCT. 61 (77·2% [95% CI 66·1-86·6]) patients achieved a complete response. During induction treatment, the most common grade 3 toxicity was anaemia (37 [47%]) and the most common grade 4 toxicity was thrombocytopenia (50 [63%]). During HCT-ASCT, the most common grade 3 toxicity was fever (50 [68%] of 73) and the most common grade 4 toxicity was leucopenia (68 [93%] of 73). We recorded four (5%) treatment-related deaths (three [4%] during induction and one [1%] 4 weeks after HCT-ASCT). HCT-ASCT with thiotepa and carmustine is an effective treatment option in young patients with newly diagnosed primary CNS lymphoma, but further comparative studies are needed. University Hospital Freiburg and Amgen.

Cardiorespiratory fitness in long-term lymphoma survivors after high-dose chemotherapy with autologous stem cell transplantation

Background:Cardiorespiratory fitness as measured by peak oxygen consumption (VO2peak) is a strong predictor of longevity and may be compromised by anticancer therapy, inactivity, and smoking. We compared VO2peak among lymphoma survivors (LSs) with reference data from healthy sedentary subjects, after a 10.2-year (mean) follow-up post high-dose chemotherapy with autologous stem cell transplantation (HDT-ASCT). We further examined the association between VO2peak and treatment, physical activity, smoking, pulmonary, and cardiac function.Methods:Lymphoma survivors treated with HDT-ASCT in Norway 1987–2008 were eligible. VO2peak was assessed by cardiopulmonary exercise testing. Pulmonary function testing and echocardiography were also conducted. Data on treatment, physical activity, and smoking were collected from hospital records and questionnaires. VO2peak was compared with age–sex predicted reference data. Linear regression was used to associate clinical factors with VO2peak cross-sectionally.Results:A total of 194 LSs without heart failure were studied. Mean VO2peak was 4.5% and 7.7% below norms in females and males, respectively. Twenty-two percent had impaired (<80% predicted) VO2peak. Decreasing VO2peak was associated with impaired diffusion capacity and current smoking, while physical activity level and VO2peak were positively associated.Conclusion:We suggest increased attention towards physical activity counseling and smoking cessation advice to preserve cardiorespiratory fitness in LSs after HDT-ASCT. Patients with impaired diffusion capacity may benefit from subsequent monitoring to detect pulmonary vascular diseases.